Bv8 is a small protein that was originally isolated from the skin secretions of the frog Bombina variegata (Mollay et al., Eur. J. Pharmacol., 374:189-196 (1999)). Bv8 belongs to a structurally related class of peptides that includes endocrine gland derived vascular endothelial growth factor (EG-VEGF) (LeCouter et al., Nature, 412:877-884 (2001)). A distinguishing structural motif of these molecules is a colipase-fold, where 10 cysteine residues form five disulfide bridges within a conserved span.
Bv8 and EG-VEGF are homologs of vascular endothelial growth factor (VEGF), an angiogenic factor known to have an important role in tumor growth and survival. Both Bv8 and EG-VEGF have been identified as angiogenic factors with selective activities for endothelial cells of specific tissues. EG-VEGF promoted proliferation, migration, survival, and fenestration in cultured adrenal capillary endothelial cells and induced angiogenesis in ovary and testis. LeCouter et al., 2001, Nature, 412:877-884; LeCouter et al., 2003, Proc. Natl. Acad. Sci. USA, 100:2685-2690.
Like EG-VEGF, Bv8 promoted proliferation, survival, and migration of adrenal cortical capillary endothelial cells and induced angiogenesis in testis. LeCouter et al., 2003, Proc. Natl. Acad. Sci. USA, 100:2685-2690. The testis exhibits relatively high turnover of endothelial cells. Thus, Bv8 and EG-VEGF, along with other factors such as VEGF, are considered to be important in maintaining the integrity and regulating proliferation of the blood vessels in the testis.
VEGF is an angiogenic factor known to have an important role in tumor growth and survival. Because Bv8 and EG-VEGF are angiogenic factors with selective activity for specific tissues, it is desirable to further characterize the molecules.